2-amino-7,7-dimethyl-5-oxo-4-(2-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile | 304880-15-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-7,7-dimethyl-5-oxo-4-(2-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
• 英文别名: 2-amino-7,7-dimethyl-5-oxo-4-[2-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile；2-amino-7,7-dimethyl-5-oxo-4-[2-(trifluoromethyl)phenyl]-6,8-dihydro-4H-chromene-3-carbonitrile
• CAS: 304880-15-7
• 化学式: C₁₉H₁₇F₃N₂O₂
• 分子量: 362.351
• InChiKey: FWOCSUIYRBGOTM-UHFFFAOYSA-N

物化性质

• 熔点：
  218-220 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  527.1±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-amino-7,7-dimethyl-5-oxo-4-(2-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile 在 碘苯二乙酸 作用下， 以 三氟乙酸 为溶剂， 反应 0.5h， 以84%的产率得到C₁₉H₁₄F₃NO₃
  参考文献：
  名称：

  高价碘促进 4H-色烯转化为二氢呋喃和 2H-色烯

  摘要：

  摘要 在环境温度下通过一锅反应完成了在高价碘的作用下将 4H-色烯合成转化为二氢呋喃 (3) 和 2H-色烯 (11) 的新方案。二氢呋喃仅在碱性反应条件下形成，而 2H-色烯是在酸性条件下的产物。具有广泛的底物范围（包括各种杂环和高产率）的简单反应条件是该协议的吸引人的特点。图形概要

  DOI：

  10.1080/00397911.2020.1799013
• 作为产物：
  描述：

  邻三氟甲基苯甲醛 在 哌啶 作用下， 以 甲醇 为溶剂， 生成 2-amino-7,7-dimethyl-5-oxo-4-(2-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  New multipotent tetracyclic tacrines with neuroprotective activity

  摘要：

  The synthesis and the biological evaluation (neuroprotection, voltage dependent calcium channel blockade, AChE/ BuChE inhibitory activity and propidium binding) of new multipotent tetracyclic tacrine analogues (5-13) are described. Compounds 7, 8 and 11 showed a significant neuroprotective effect on neuroblastoma cells subjected to Ca2+ overload or free radical induced toxicity. These compounds are modest AChE inhibitors [the best inhibitor (11) is 50-fold less potent than tacrine], but proved to be very selective, as for most of them no BuChE inhibition was observed. In addition, the propidium. displacement experiments showed that these compounds bind AChE to the peripheral anionic site (PAS) of AChE and, consequently, are potential agents that can prevent the aggregation of P-amyloid. Overall, compound 8 is a modest and selective AChE inhibitor, but an efficient neuroprotective agent against 70 mM K+ and 60 mu M H2O2. Based on these results, some of these molecules can be considered as lead candidates for the further development of anti-Alzheimer drugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.025

文献信息

• One-pot synthesis of tetrahydrochromene derivatives catalyzed by lipase
  作者：Jiang-Cheng Xu、Wan-Mei Li、Hui Zheng、Yi-Feng Lai、Peng-Fei Zhang

  DOI：10.1016/j.tet.2011.09.137

  日期：2011.12

  An efficient and green one-pot synthesis route for tetrahydrochromene derivatives was developed. Lipase from Porcine pancreas (PPL) shows excellent catalytic activity and exerts good adaptability to different substrates in the reaction. All the reactions go smoothly and provide tetrahydrochromene derivatives with isolate yield up to 97% under room temperature. This lipase-catalyzed multistep conversion

  开发了一种高效，绿色的一锅合成四氢萘衍生物的路线。来自猪胰腺（PPL）的脂肪酶显示出优异的催化活性，并且对反应中的不同底物表现出良好的适应性。所有反应均进行顺利，并在室温下提供分离度高达97％的四氢苯并二氢萘衍生物。这种脂肪酶催化的多步转化方法为合成色烯衍生物提供了新的策略，并扩展了酶在有机合成中的应用。
• Group-assisted purification (GAP) chemistry for dihydrofurans: water as a medium for catalyst free synthesis in a one pot four component reaction
  作者：Madhu Chennapuram、Narender Reddy Emmadi、Chiranjeevi Bingi、Jagadeesh Babu Nanubolu、Krishnaiah Atmakur

  DOI：10.1039/c4gc00388h

  日期：——

  A simple, catalyst free, water mediated, one pot four component, green protocol was developed for title compounds 7 starting from aromatic aldehydes (1), malononitrile (2), 1,3-diones (3) and N-chlorosuccinimide (NCS) in a sequential addition reaction at ambient temperature. The approach presented herein, for the first time, is through an unusual rearrangement where NCS was reacted with 2-amino-7,

  为标题化合物7开发了一种简单的，无催化剂，水介导的，一锅四组分的绿色方案，起始于芳族醛（1），丙二腈（2），1,3-二酮（3）和N-氯代琥珀酰亚胺（NCS）在室温下按顺序加成反应。本文首次提出的方法是通过不寻常的重排，其中NCS与2-氨基-7,7-二甲基-5-氧代-4-芳基-5,6,7,8-四氢-4 H反应-chromene-3-carbontritrile（4），它是由醛和丙二腈的Knoevenagel缩合，然后迈克尔加成3形成的。此外，这种新颖的方案与各种醛和具有活性的C–H功能衍生物兼容，可实现高收率并遵循GAP化学原理。有趣的是，化合物4与NCS在酒精介质中反应时，得到2-氰基-6,6-二甲基-4-氧代-3-芳基-2,3,4,5,6,7-六氢苯并呋喃-2-羧酸酯（5） 。
• Molecular-Iodine-Promoted Synthesis of Dihydrobenzofuran-3,3-dicarbonitriles through a Novel Rearrangement
  作者：Nagaraju Medishetti、Ashok Kale、Jagadeesh Nanubolu、Krishnaiah Atmakur

  DOI：10.1055/s-0037-1611706

  日期：2019.2

  by molecular iodine in basic medium via 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, by a novel protocol. The protocol involves a novel rearrangement in which the 4H-chromene fragment dissociates to a cyclopropane moiety and rearranges to the five-membered compound 6,6-dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzofuran-3,3(2H)-dicarbonitrile. Simple reaction conditions

  标题化合物由 5,5-二甲基环己烷-1,3-二酮、苯甲醛和丙二腈在碱性介质中通过 2-氨基-7,7-二甲基-5-氧代-4-苯基-5 催化合成， 6,7,8-四氢-4H-色烯-3-腈，通过一种新的协议。该协议涉及一种新的重排，其中 4H-色烯片段解离为环丙烷部分并重排为五元化合物 6,6-二甲基-4-氧代-2-苯基-4,5,6,7-四氢苯并呋喃- 3,3(2H)-二腈。该协议的优点是反应条件简单、产率高、兼容性好。
• New multipotent tetracyclic tacrines with neuroprotective activity
  作者：José Marco-Contelles、Rafael León、Cristóbal de los Ríos、Antonio G. García、Manuela G. López、Mercedes Villarroya

  DOI：10.1016/j.bmc.2006.09.025

  日期：2006.12

  The synthesis and the biological evaluation (neuroprotection, voltage dependent calcium channel blockade, AChE/ BuChE inhibitory activity and propidium binding) of new multipotent tetracyclic tacrine analogues (5-13) are described. Compounds 7, 8 and 11 showed a significant neuroprotective effect on neuroblastoma cells subjected to Ca2+ overload or free radical induced toxicity. These compounds are modest AChE inhibitors [the best inhibitor (11) is 50-fold less potent than tacrine], but proved to be very selective, as for most of them no BuChE inhibition was observed. In addition, the propidium. displacement experiments showed that these compounds bind AChE to the peripheral anionic site (PAS) of AChE and, consequently, are potential agents that can prevent the aggregation of P-amyloid. Overall, compound 8 is a modest and selective AChE inhibitor, but an efficient neuroprotective agent against 70 mM K+ and 60 mu M H2O2. Based on these results, some of these molecules can be considered as lead candidates for the further development of anti-Alzheimer drugs. (c) 2006 Elsevier Ltd. All rights reserved.
• Hypervalent iodine promoted transformation of 4<i>H</i>-chromenes into dihydrofurans and 2<i>H</i>-chromenes
  作者：Ashok Kale、Nagaraju Medishetti、Jagadeesh Babu Nanubolu、Krishnaiah Atmakur

  DOI：10.1080/00397911.2020.1799013

  日期：2020.11.1

  Abstract A novel protocol to synthetic transformation of 4H-chromenes into dihydrofurans (3) and 2H-chromenes (11) promoted by hypervalent iodine has been accomplished in a one-pot reaction at ambient temperature. Dihydrofurans are exclusively formed under basic reaction conditions, whereas, 2H-chromenes are the products under acidic condition. Simple reaction conditions with a broad substrate scope

  摘要 在环境温度下通过一锅反应完成了在高价碘的作用下将 4H-色烯合成转化为二氢呋喃 (3) 和 2H-色烯 (11) 的新方案。二氢呋喃仅在碱性反应条件下形成，而 2H-色烯是在酸性条件下的产物。具有广泛的底物范围（包括各种杂环和高产率）的简单反应条件是该协议的吸引人的特点。图形概要